1. Field of the Invention
Embodiments of the invention relate to methods of altering sympathetic nerve firing and augmenting cerebral blood flow. Methods are described for treatment of individuals in need of augmented cerebral blood flow, such as during and after stroke, transient ischemic attack and myocardial infarction.
2. Description of the Related Art
Therapeutic hypothermia is the use of hypothermia to cool the brain to provide neuroprotection. Therapeutic hypothermias have potential for treating ischemic insult when the brain is deprived of oxygen by cardiac arrest, stroke or brain trauma.
Animal studies have shown therapeutic hypothermia to be an effective neuroprotectant (Krieger, Derk. et al. “Cooling for Acute Ischemic Brain Damage.” American Heart Association. May 25, 2001, pg. 1847-1854) and that cooling the ischemic brain can provide neuroprotection (Polderman, Kees H. “Application of therapeutic hypothermia in the ICU.” Intensive Care Med. (2004) 30:556-575).
Therapeutic hypothermia has been endorsed by the American Heart Association (AHA) and International Liason Committee on Resuscitation (ILCOR) for use after cardiac arrest. In one study, patients resuscitated 5-15 min. after collapse were cooled over a 24 hour period at a target temperature of 32-34° C. The group receiving the therapeutic hypothermia had a death rate that was 14% lower than the group receiving standard care (Holzer, Michael “Mild Hypothermia to Improve the Neurologic Outcome After Cardiac Arrest.” New England Journal of Medicine. (2002) Vol. 346, No. 8).
While it is known that mild hypothermia (32-34° C. (89.6-93.2° F.)) is effective in treatment of ischemia, there are problems with lowering body temperature to 32-34° C. One problem is that normally at around 36° C. (96.8° F.) the patient will begin to shiver and drugs such as Desflurane and Demerol must be administered to inhibit the shiver response. Other side effects include arrhythmia, decreased clotting threshold, increased risk of infection, and electrolyte imbalance. Furthermore, the physician must take care to rewarm the patient gradually to avoid spikes in intracranial pressure.
Furthermore, body cooling is generally accomplished by either an invasive method such as a catheter or a non-invasive method such as a water blanket. There are problems with these techniques.
Cooling catheters are placed in an appropriate vein or artery. A catheter placed into the femoral vein near the heart can cool the entire body by circulating a saline solution through the catheter that is controlled by an exterior control unit. However, the technique is invasive and potentially may induce bleeding, vascular puncture, infection and deep vein thrombosis.
A non-invasive technique for lowering of body temperature is a water blanket. Water blankets may be applied by non-physician hospital personnel and do not require any insertion into the patient body. The drawbacks include danger of electric shock, freezer burns to the patient and difficulty in precisely controlling temperature.
While cold anywhere in the body can be neuroprotective, part of the neuroprotection may be due to enhanced cerebral blood flow (cbf). According to dogma, hypothermia leads to a progressive diminution of cbf, such that 1 degree reduction of body temperature results in a 10% reduction in cbf. However, several pieces of evidence suggest that the cerebrovascular response to cold may be biphasic and possibly even dependent on the mode of cooling.
U.S. Pat. No. 6,942,686 discloses regulation of cerebral blood flow by cooling or heating of an artery of the patient. U.S. Pat. No. 6,942,686 teaches relatively large temperature changes (cooling to 30° C. or below) in order to enhance cerebral blood flow.
It has been found by the inventors that very small decreases in body temperature (up to 1.5° C.) produce unexpectedly large increases in cbf. Furthermore, the increase in cbf was achieved without the necessity of lowering basal body temperature. Augmentation of cbf was achieved by selectively cooling only a part of the body such as the nose and/or mouth. Methods of enhancing cbf are disclosed with implications for treatment of ischemia.